EP1488785A1 - Emulsion à l'huile pour la substitution postnatale des hormones - Google Patents
Emulsion à l'huile pour la substitution postnatale des hormones Download PDFInfo
- Publication number
- EP1488785A1 EP1488785A1 EP03013790A EP03013790A EP1488785A1 EP 1488785 A1 EP1488785 A1 EP 1488785A1 EP 03013790 A EP03013790 A EP 03013790A EP 03013790 A EP03013790 A EP 03013790A EP 1488785 A1 EP1488785 A1 EP 1488785A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- oil
- emulsion
- hormones
- estrogen
- oil emulsion
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/34—Gestagens
Definitions
- the invention relates to a process for the preparation of hormone-containing oil emulsions (Lipid emulsions), an isotonic oil emulsion obtainable by this method as well as the use of the emulsion according to the invention for the preparation of a Drug for intravenous administration, especially for postnatal Hormone replacement in premature babies and for the treatment of neurological Damage after strokes.
- hormone-containing oil emulsions Lipid emulsions
- isotonic oil emulsion obtainable by this method as well as the use of the emulsion according to the invention for the preparation of a Drug for intravenous administration, especially for postnatal Hormone replacement in premature babies and for the treatment of neurological Damage after strokes.
- Transepidermal treatment with the corresponding hormones is in principle possible, but for development-specific reasons only 2 - 3 weeks be started postnatal.
- Intralipid® sold lipid emulsion added and administered.
- the oil phase of Intralipid® consists of 100% soybean oil in the form long-chain triglycerides.
- the problem underlying the invention is therefore the provision of parenterally administrable oil emulsions with minimal oil and volume delivery to the highest possible accumulation of hormones (availability) in the blood of the Premature babies lead.
- Another embodiment of the invention relates to a hormone-containing isotonic Oil emulsion for intravenous administration, obtainable by the above method is.
- a hormone-containing isotonic Oil emulsion for intravenous administration obtainable by the above method is.
- the O / W emulsions according to the invention are for the parenteral, in particular suitable for intravenous administration. Accordingly, a third concerns Embodiment of the invention the use of the above isotonic oil emulsion for intravenous administration, especially for postnatal hormone replacement Preterm infants.
- oil and lipid are in the context of the present invention of identical meaning and are therefore used interchangeably. Under this Group are in particular triglycerides, partial glycerides and fatty acid residues and understand their mixtures.
- the oil emulsions according to the invention are particularly suitable for processes for Preparation of drugs for parenteral administration of estrogens and Progestogens, preferably for postnatal hormone replacement in premature babies.
- the goal of the postnatal substitution of progestogen and estrogen is the maintenance of intrauterine plasma concentrations (plasma concentration in utero ). In order to deviate as little as possible from the intrauterine plasma concentrations after birth, their fastest possible attainment after the beginning of the substitution is desirable.
- Hormone replacement is not limited to human premature babies, but can also be applied to animals, preferably mammals.
- the oil emulsions of the invention have a much better availability the hormones contained therein compared to those of an oil emulsion of the state the technology.
- the oil emulsion according to the invention leads, compared with emulsions of the prior Technology, to a faster increase in hormone levels and to one higher estrogen final concentration with lower volume and oil intake.
- oil emulsions according to the invention have improved stability compared with the alcoholic hormone solutions of the prior art.
- the decisive step of the process according to the invention for the preparation of Oil emulsions is the release of the hormones estradiol and progesterone in the oil phase before emulsifying the oil phase with the water phase.
- both Hormones dissolved in the oil phase.
- only one of the hormones, preferably an estrogen, is dissolved in the oil phase, while the gestagen is added to the water phase and / or the finished emulsion becomes.
- the hormones used in connection with the present invention are those that also occur intrauterine.
- Follicular hormones are estrone, 17- ⁇ -estradiol and estriol and their derivatives. Due to its high estrogenic activity, 17 ⁇ -oestradiol is known for its present invention of particular importance.
- Corporal hormones include pregnelonone, progesterone, medroxyprogesterone and theirs pharmaceutically acceptable derivatives wherein progesterone is associated with is preferably used in the present invention.
- An embodiment of the invention relates to the combination of estrone with Pregnelonone and / or progesterone, another the combination of estriol with Pregnelonone and / or progesterone.
- An alternative, more preferred Embodiment relates to the combination of 17- ⁇ -estradiol and / or pregnelonone and / or progesterone, especially with progesterone.
- the lipid emulsions according to the invention have hormone concentrations which are at appropriate use lead to concentrations in the premature infant, as they in the womb would have been expected. Consequently, the inventive Lipid emulsion between 0.005 and 0.5 wt .-%, preferably between 0.01 and 0.2 Wt .-%, particularly preferably between 0.05 and 0.1 wt .-% of at least one Estrogens and between 0.05 and 5 wt .-%, preferably between 0.1 and 2 Wt .-%, particularly preferably between 0.5 and 1 wt .-% of at least one Gestagen, based on the total composition (parent emulsion).
- the ratio of progestin to estrogen in the emulsion is 2: 1 to 200: 1, preferably 5: 1 to 50: 1, more preferably 10: 1 to 20: 1.
- the parent emulsions if necessary with an appropriate amount, preferably up to four times the amount Water to be diluted.
- the lipid emulsions according to the invention are preferably made from vegetable oils Origin (e.g., safflower oil or soybean oil) and / or MCT and / or animal oils Made of origin. You can therefore use vegetable oil and / or medium-chain Triglycerides (MCT) and / or oils of marine origin (e.g., fish oils). Such lipid emulsions are known to those skilled in the art.
- vegetable oils Origin e.g., safflower oil or soybean oil
- MCT medium-chain Triglycerides
- marine origin e.g., fish oils
- Vegetable oils and in particular the oils of soybean and safflower thistle are by a high proportion of polyunsaturated fatty acids from the ⁇ -6 series characterized (predominantly linoleic acid, 18: 2 ⁇ -6), while their content of ⁇ -3 fatty acids (practically exclusively as ⁇ -linolenic acid, 18: 3 ⁇ -3) is low.
- MCT Medium chain triglycerides
- the medium-chain triglycerides (MCT) administered with the oil emulsions serve mainly as an energy source.
- MCT medium-chain triglycerides
- Medium chain triglycerides do not contain any unsaturated fatty acids and thus neither ⁇ -6 nor ⁇ -3 fatty acids.
- the fish oils obtained from cold-water fish are characterized by a high proportion of polyunsaturated fatty acids (mainly Eicosapentaenoic acid, EPA, 20: 5 ⁇ -3 and docosahexaenoic acid, DHA, 22: 6 ⁇ -3), while their content of ⁇ -6 fatty acids is low.
- Suitable fish oils are for example, those that are technically significant Cold water fish are obtained.
- Fish oils generally contain triglycerides of fatty acids with 12 to 22 carbon atoms.
- Particularly preferred Highly purified fish oil concentrates for example from sardine oil, salmon oil, Herring oil and / or mackerel oil are obtained.
- An embodiment of the invention therefore relates to an oil emulsion based of vegetable oil and / or MCT.
- This emulsion may optionally comprise fish oil.
- the proportion of vegetable oil in the oil composition according to the invention is while at least 50 to 100 wt .-%, preferably 70 to 100 wt .-%, especially preferably 90 to 100 wt .-% based on the oil composition.
- the total oil content of the parent emulsion is between 1% by weight and 30% by weight, Preferably between 10 wt .-% and 20 wt .-%, based on the aqueous Oil emulsion.
- the isotonic oil emulsion can in addition to distilled water nor the usual auxiliary and / or Additives such as emulsifiers, emulsifiers (co-emulsifiers), Stabilizers, antioxidants and IsotonmaschineszuA included.
- Suitable emulsifiers are physiologically compatible emulsifiers, such as phospholipids animal or vegetable origin. Particularly preferred purified lecithins, especially egg lecithin or fractions thereof or the corresponding phosphatides.
- the emulsifier content is 0.6% by weight to 1.5 Wt .-%, preferably 1.2 wt .-% based on the total emulsion.
- Alkali salts of long-chain C 16 to C 20 fatty acids can furthermore be used as emulsifying auxiliaries. Particularly preferred are their sodium salts.
- the emulsifying aids are used in a concentration of 0.005 wt .-% to 0.1 wt .-%, preferably from 0.01 wt .-% to 0.5 wt .-%, based on the total emulsion.
- the emulsion according to the invention of 1.0 Wt% to 8 wt%, preferably 2.0 wt% to 6.0 wt%, especially preferably 2.2 wt .-% to 2.6 wt .-% of a stabilizing or Isotonmaschineszusatzes, for example, a polyhydric alcohol containing.
- a stabilizing or Isotontechnischszusatzes for example, a polyhydric alcohol containing.
- Preferred in this context is glycerol, glucose, or xylitol, wherein Glycerol is particularly preferred.
- the oil emulsion according to the invention can be used as antioxidant and thus for protection Peroxide formation Tocopherols or physiologically acceptable tocopherol esters, e.g. alpha-tocopherol acetate, in an amount of 10 to 1000 mg, preferably 25 to 200 mg, based on 100 g of oil.
- Peroxide formation Tocopherols or physiologically acceptable tocopherol esters, e.g. alpha-tocopherol acetate, in an amount of 10 to 1000 mg, preferably 25 to 200 mg, based on 100 g of oil.
- the oil emulsions according to the invention contain no Preservatives, e.g. Benzyl alcohol.
- the oil emulsions according to the invention are always oil-in-water (O / W) emulsions, in which the outer, coherent phase out distilled water suitable for parenteral use.
- the oil emulsion advantageously has a pH of 6.0 to 9.0, preferably from 6.5 to 8.5 on.
- the isotonic aqueous lipid emulsions according to the invention can be prepared by known methods Process are produced. Usually one proceeds in such a way that one First, the oils, the emulsifier and other auxiliaries and additives together mixed and then filled while dispersing with water.
- the water can optionally further containing other water-soluble components (e.g., glycerin).
- the emulsion thus obtained still has droplet sizes of about 10 microns.
- the average droplet size of the emulsion must be determined by further homogenization e.g. be further reduced by using a high-pressure homogenizer.
- Preferred for parenteral, especially for intravenous use Droplet sizes with an average particle diameter of 0.5 ⁇ m to 150 nm, more preferably 1 .mu.m to 100 nm.
- the solutions are intended beyond that sterilizable and stable storage for at least 18 months.
- the oil emulsions of the invention the Dying of nerve cells in the brain of humans and animals, preferably Reduce mammals and therefore also for the production of medicines Treatment of neurological damage after strokes (apoplex) used can be.
- the oil emulsions according to the invention can also be prophylactic be applied. In such cases, oral administration of the To prefer oil emulsions.
- the isotonic oil emulsion of the present invention can be used in methods of hormone replacement in preterm infants as well as for the treatment of neurological damage Strokes are applied.
- Solution I is added to Component II using an Ultra-Terrax.
- the pH of the resulting o / w emulsion is adjusted to about 8.5 by the addition of sodium oleate.
- the mixture is then homogenized in a high-pressure homogenizer at at least 400 kg / cm 2 .
- the patient group treated with a hormone emulsion of the prior art consisted of 12 patients (preterm infants ⁇ 29 Pregnancy weeks, birth weight below 1000 g). This was with a Hormone emulsion consisting of 20% by weight of Intralipid® (Pharmacia & Upjohn, Germany) diluted with isotonic saline solution to 5% oil content with an ethanolic solution of 0.15 mg / ml crystalline 17 ⁇ -estradiol and 1.4 mg / mL progesterone was treated.
- Intralipid® Pulharmacia & Upjohn, Germany
- the initial feed was continuously i.v. at 15 ml / kg / day. began. Both the Hormone content of the emulsion as well as the amount of liquid could be varied. This resulted in fluid supplies up to a maximum of 25.8 ml / kg / day, median 18.8).
- Table 1 shows the median supply of estradiol and progesterone until the 14th Day of life for the premature babies of both groups. Both emulsions resulted a similar high hormone intake. While the emulsion of the invention was fed at a constant rate of 15 ml / kg / day, the emulsion of the prior art was Median technique at 18.8 ml / kg / day (min-max: 11.4 to 25.8 ml / kg / day) administered.
- the available data indicates better availability of estradiol and progesterone measured by the plasma concentrations achieved in premature babies.
- the emulsion according to the invention is used in premature babies better than the comparable emulsion of the prior Technique made by mixing the hormones with the finished emulsion has been.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Steroid Compounds (AREA)
Priority Applications (16)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03013790A EP1488785A1 (fr) | 2003-06-18 | 2003-06-18 | Emulsion à l'huile pour la substitution postnatale des hormones |
BRPI0410558-3A BRPI0410558A (pt) | 2003-06-18 | 2004-06-15 | processo para a preparação de emulsões oleosas isotÈnicas, emulsão oleosa isotÈnica, uso da mesma, e, processos para reposição de hormÈnio em bebês prematuros, e para o tratamento de danos neurológicos após derrames |
RU2006101322/15A RU2318494C2 (ru) | 2003-06-18 | 2004-06-15 | Масляная эмульсия для послеродового замещения гормона |
ES04741802T ES2281813T3 (es) | 2003-06-18 | 2004-06-15 | Emulsion para la sustitucion hormonal postnatal. |
AT04741802T ATE359061T1 (de) | 2003-06-18 | 2004-06-15 | Emulsion zur postnatalen hormonsubstitution |
PL04741802T PL1633325T3 (pl) | 2003-06-18 | 2004-06-15 | Emulsja do poporodowej substytucji hormonalnej |
EP04741802A EP1633325B1 (fr) | 2003-06-18 | 2004-06-15 | Emulsion d'huile pour la substitution hormonale postnatale |
PCT/EP2004/051114 WO2004110402A1 (fr) | 2003-06-18 | 2004-06-15 | Emulsion d'huile pour la substitution hormonale postnatale |
AU2004246823A AU2004246823B2 (en) | 2003-06-18 | 2004-06-15 | Oil emulsion for postnatal hormone substitution |
CA002526567A CA2526567A1 (fr) | 2003-06-18 | 2004-06-15 | Emulsion d'huile pour la substitution hormonale postnatale |
JP2006516152A JP2006527736A (ja) | 2003-06-18 | 2004-06-15 | 出生後ホルモン置換のためのオイルエマルジョン |
CN2004800170774A CN1809339B (zh) | 2003-06-18 | 2004-06-15 | 用于出生后荷尔蒙替代品的油乳状液 |
MXPA05012411A MXPA05012411A (es) | 2003-06-18 | 2004-06-15 | Emulsion oleosa para sustitucion postnatal de hormonas. |
US10/561,631 US20070071777A1 (en) | 2003-06-18 | 2004-06-15 | Oil emulsion for postnatal hormone substitution |
DE502004003483T DE502004003483D1 (de) | 2003-06-18 | 2004-06-15 | Emulsion zur postnatalen hormonsubstitution |
PT04741802T PT1633325E (pt) | 2003-06-18 | 2004-06-15 | Emulsão para substituição hormonal pós-parto |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03013790A EP1488785A1 (fr) | 2003-06-18 | 2003-06-18 | Emulsion à l'huile pour la substitution postnatale des hormones |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1488785A1 true EP1488785A1 (fr) | 2004-12-22 |
Family
ID=33395816
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP03013790A Withdrawn EP1488785A1 (fr) | 2003-06-18 | 2003-06-18 | Emulsion à l'huile pour la substitution postnatale des hormones |
EP04741802A Expired - Lifetime EP1633325B1 (fr) | 2003-06-18 | 2004-06-15 | Emulsion d'huile pour la substitution hormonale postnatale |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP04741802A Expired - Lifetime EP1633325B1 (fr) | 2003-06-18 | 2004-06-15 | Emulsion d'huile pour la substitution hormonale postnatale |
Country Status (14)
Country | Link |
---|---|
US (1) | US20070071777A1 (fr) |
EP (2) | EP1488785A1 (fr) |
JP (1) | JP2006527736A (fr) |
CN (1) | CN1809339B (fr) |
AT (1) | ATE359061T1 (fr) |
BR (1) | BRPI0410558A (fr) |
CA (1) | CA2526567A1 (fr) |
DE (1) | DE502004003483D1 (fr) |
ES (1) | ES2281813T3 (fr) |
MX (1) | MXPA05012411A (fr) |
PL (1) | PL1633325T3 (fr) |
PT (1) | PT1633325E (fr) |
RU (1) | RU2318494C2 (fr) |
WO (1) | WO2004110402A1 (fr) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011134937A3 (fr) * | 2010-04-26 | 2012-02-02 | Besins Healthcare Luxembourg Sarl | Compositions d'émulsion pharmaceutique comprenant du progestogène |
US20150011515A1 (en) * | 2012-02-29 | 2015-01-08 | B. Braun Melsungen Ag | Hormone Containing Emulsion |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8367647B2 (en) * | 2007-06-21 | 2013-02-05 | Pantarhei Bioscience B.V. | Treatment of meconium aspiration syndrome with estrogens |
CN102202672A (zh) * | 2008-10-10 | 2011-09-28 | 达拉生物科学公司 | 使用穗霉素衍生物治疗或预防疼痛的方法 |
US8993625B2 (en) | 2009-03-11 | 2015-03-31 | Stable Solutions Llc | Method of mitigating adverse drug events using omega-3 fatty acids as a parenteral therapeutic drug vehicle |
US9034389B2 (en) | 2009-03-11 | 2015-05-19 | Stable Solutions Llc | Omega-3 enriched fish oil-in-water parenteral nutrition emulsions |
US20110200644A1 (en) * | 2010-02-18 | 2011-08-18 | Martek Biosciences Corporation | DHA Ester Emulsions |
US20110200645A1 (en) * | 2010-02-18 | 2011-08-18 | Martek Biosciences Corporation | DHA Free Fatty Acid Emulsions |
WO2011103514A1 (fr) * | 2010-02-18 | 2011-08-25 | Martek Biosciences Corporation | Émulsions de triglycéride dha |
EP2544707B1 (fr) * | 2010-03-09 | 2018-11-21 | Dignity Health | Procédés pour inhiber les troubles de travail prématuré et de contractilité utérine et pour prévenir la maturation cervicale |
US9301920B2 (en) | 2012-06-18 | 2016-04-05 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
EP3936133A1 (fr) | 2011-11-23 | 2022-01-12 | TherapeuticsMD, Inc. | Préparations et thérapies de substitution pour hormonothérapie naturelle combinée |
TWI651098B (zh) * | 2012-02-29 | 2019-02-21 | B 柏藍麥桑根公司 | 含荷爾蒙的乳劑 |
US10806740B2 (en) | 2012-06-18 | 2020-10-20 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US10806697B2 (en) | 2012-12-21 | 2020-10-20 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10568891B2 (en) | 2012-12-21 | 2020-02-25 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10537581B2 (en) | 2012-12-21 | 2020-01-21 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US9180091B2 (en) | 2012-12-21 | 2015-11-10 | Therapeuticsmd, Inc. | Soluble estradiol capsule for vaginal insertion |
US11246875B2 (en) | 2012-12-21 | 2022-02-15 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US11266661B2 (en) | 2012-12-21 | 2022-03-08 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
CA2947767A1 (fr) | 2014-05-22 | 2015-11-26 | Therapeuticsmd, Inc. | Formulations d'hormones substitutives combinees naturelles et traitement hormonal substitutif |
EP3193830B1 (fr) | 2014-09-19 | 2023-11-01 | Heron Therapeutics, Inc. | Emulsion d'aprepitant |
US9974742B2 (en) | 2016-02-01 | 2018-05-22 | Heron Therapeutics, Inc. | Emulsion formulations of an NK-1 receptor antagonist and uses thereof |
US10285998B1 (en) | 2018-04-04 | 2019-05-14 | The Menopause Method, Inc. | Composition and method to aid in hormone replacement therapy |
US11633405B2 (en) | 2020-02-07 | 2023-04-25 | Therapeuticsmd, Inc. | Steroid hormone pharmaceutical formulations |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0391369A2 (fr) * | 1989-04-05 | 1990-10-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Emulsions pour médicaments |
WO1994022426A1 (fr) * | 1993-04-07 | 1994-10-13 | Astra Aktiebolag | Composition pharmaceutique contenant des medicaments lipophiles |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS60258110A (ja) * | 1984-06-05 | 1985-12-20 | Daigo Eiyou Kagaku Kk | 静脈注射可能なプロゲステロン乳化注射液 |
CN1029293C (zh) * | 1993-01-01 | 1995-07-12 | 浙江省中医院 | 薏苡仁中性油脂乳剂 |
US6267985B1 (en) * | 1999-06-30 | 2001-07-31 | Lipocine Inc. | Clear oil-containing pharmaceutical compositions |
CN1204238C (zh) * | 2000-10-18 | 2005-06-01 | 李大鹏 | 从核桃仁中提取的核桃仁油组合物及其药物制剂 |
-
2003
- 2003-06-18 EP EP03013790A patent/EP1488785A1/fr not_active Withdrawn
-
2004
- 2004-06-15 DE DE502004003483T patent/DE502004003483D1/de not_active Expired - Lifetime
- 2004-06-15 ES ES04741802T patent/ES2281813T3/es not_active Expired - Lifetime
- 2004-06-15 PL PL04741802T patent/PL1633325T3/pl unknown
- 2004-06-15 PT PT04741802T patent/PT1633325E/pt unknown
- 2004-06-15 JP JP2006516152A patent/JP2006527736A/ja active Pending
- 2004-06-15 RU RU2006101322/15A patent/RU2318494C2/ru active
- 2004-06-15 MX MXPA05012411A patent/MXPA05012411A/es active IP Right Grant
- 2004-06-15 WO PCT/EP2004/051114 patent/WO2004110402A1/fr active IP Right Grant
- 2004-06-15 CA CA002526567A patent/CA2526567A1/fr not_active Abandoned
- 2004-06-15 BR BRPI0410558-3A patent/BRPI0410558A/pt not_active Application Discontinuation
- 2004-06-15 CN CN2004800170774A patent/CN1809339B/zh not_active Expired - Fee Related
- 2004-06-15 EP EP04741802A patent/EP1633325B1/fr not_active Expired - Lifetime
- 2004-06-15 AT AT04741802T patent/ATE359061T1/de not_active IP Right Cessation
- 2004-06-15 US US10/561,631 patent/US20070071777A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0391369A2 (fr) * | 1989-04-05 | 1990-10-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Emulsions pour médicaments |
WO1994022426A1 (fr) * | 1993-04-07 | 1994-10-13 | Astra Aktiebolag | Composition pharmaceutique contenant des medicaments lipophiles |
Non-Patent Citations (3)
Title |
---|
ALKAYED NABIL J ET AL: "Neuroprotective effects of female gonadal steroids in reproductively senescent female rats.", STROKE., vol. 31, no. 1, January 2000 (2000-01-01), pages 161 - 168, XP002254228, ISSN: 0039-2499 * |
KREJZA JAROSLAW ET AL: "Effect of endogenous estrogen on blood flow through carotid arteries.", STROKE, vol. 32, no. 1, January 2001 (2001-01-01), pages 30 - 36, XP002254229, ISSN: 0039-2499 * |
TROTTER A ET AL: "Effects of postnatal estradiol and progesterone replacement in extremely preterm infants.", THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. UNITED STATES DEC 1999, vol. 84, no. 12, December 1999 (1999-12-01), pages 4531 - 4535, XP002254227, ISSN: 0021-972X * |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011134937A3 (fr) * | 2010-04-26 | 2012-02-02 | Besins Healthcare Luxembourg Sarl | Compositions d'émulsion pharmaceutique comprenant du progestogène |
WO2011134944A3 (fr) * | 2010-04-26 | 2012-02-09 | Besins Healthcare Luxembourg Sarl | Compositions d'émulsion pharmaceutique à faible teneur en huile comprenant du progestogène |
CN102946864A (zh) * | 2010-04-26 | 2013-02-27 | 博赏医药卢森堡责任有限公司 | 包含孕激素的药物乳液组合物 |
US8476252B2 (en) | 2010-04-26 | 2013-07-02 | Besins Healthcare Luxembourg Sarl | Pharmaceutical emulsion compositions comprising progestogen |
US8765149B2 (en) | 2010-04-26 | 2014-07-01 | Besins Healthcare Luxembourg Sarl | Low-oil pharmaceutical emulsion compositions comprising progestogen |
EP2801353A1 (fr) * | 2010-04-26 | 2014-11-12 | Besins Healthcare Luxembourg | Compositions d'émulsions pharmaceutiques comprenant un progestogène |
EP2857042A1 (fr) * | 2010-04-26 | 2015-04-08 | Besins Healthcare Luxembourg | Compositions d'émulsion pharmaceutique à faible teneur en huile comportant du progestogène |
EA022460B1 (ru) * | 2010-04-26 | 2016-01-29 | Безен Хелткэа Люксембург Сарл | Фармацевтические композиции в виде эмульсии с низким содержанием масла, содержащие прогестоген |
AU2011246527B2 (en) * | 2010-04-26 | 2016-09-15 | Besins Healthcare Luxembourg Sarl | Low-oil pharmaceutical emulsion compositions comprising progestogen |
US9572818B2 (en) | 2010-04-26 | 2017-02-21 | Besins Healthcare Luxembourg Sarl | Pharmaceutical emulsion compositions comprising progestogen |
US20150011515A1 (en) * | 2012-02-29 | 2015-01-08 | B. Braun Melsungen Ag | Hormone Containing Emulsion |
US9789122B2 (en) * | 2012-02-29 | 2017-10-17 | B. Braun Melsungen AS | Hormone containing emulsion |
Also Published As
Publication number | Publication date |
---|---|
RU2006101322A (ru) | 2006-06-10 |
CN1809339B (zh) | 2010-06-23 |
ATE359061T1 (de) | 2007-05-15 |
EP1633325A1 (fr) | 2006-03-15 |
PL1633325T3 (pl) | 2007-08-31 |
WO2004110402A1 (fr) | 2004-12-23 |
BRPI0410558A (pt) | 2006-06-20 |
RU2318494C2 (ru) | 2008-03-10 |
CN1809339A (zh) | 2006-07-26 |
ES2281813T3 (es) | 2007-10-01 |
JP2006527736A (ja) | 2006-12-07 |
US20070071777A1 (en) | 2007-03-29 |
EP1633325B1 (fr) | 2007-04-11 |
MXPA05012411A (es) | 2006-02-13 |
PT1633325E (pt) | 2007-05-31 |
AU2004246823A1 (en) | 2004-12-23 |
CA2526567A1 (fr) | 2004-12-23 |
DE502004003483D1 (de) | 2007-05-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1633325B1 (fr) | Emulsion d'huile pour la substitution hormonale postnatale | |
DE69823548T2 (de) | Verwendung von mehrfach ungesättigten fettsäuren zur vorbeugung von nekrotizierender enterokolitis | |
DE60129134T2 (de) | O/w emulsion | |
EP0456670B1 (fr) | EMULSION GRASSE CONTENANT DES $g(v)-3-ACIDES GRAS POUR APPLICATION INTRAPERITONEALE, SA FABRICATION ET SON UTILISATION | |
CH680789A5 (fr) | ||
KR20140131937A (ko) | 호르몬 함유 유화액 | |
DE2406621A1 (de) | Naehr-fettemulsion | |
DE69625616T2 (de) | Lipidemulsionen mit optimierter hydrolyse sowie deren verwendung | |
EP2355813B1 (fr) | Émulsion grasse pour l'alimentation artificielle de patients gravement malades en soins intensifs | |
DE3721137A1 (de) | Fettemulsion zur intravenoesen anwendung | |
EP3285749B1 (fr) | Capsule de gel contenant du stérol et un agent de solubilisation | |
EP0456106A2 (fr) | Emulsion stable pour l'administration pharmaceutique, procédé pour sa préparation et son emploi comme agent pharmaceutique | |
DE3785849T2 (de) | Jod enthaltende emulsion. | |
EP0071995B1 (fr) | Emulsion grasse pour la nutrition par voie parentérale | |
DE19900054A1 (de) | Taxane enthaltende stabile und sterile Emulsion und Verfahren zu ihrer Herstellung | |
DE3884945T2 (de) | Emulsion für parenterale verabreichung. | |
DE69428967T2 (de) | Pharmazeutische emulsionen, die bioaktive steroide enthalten | |
DE4111939C2 (fr) | ||
DE69005298T2 (de) | Arznei-lipid-zusammensetzung für parenterale nahrung. | |
DE4217842A1 (de) | Calciumantagonisten enthaltende pharmazeutische Zubereitung zur intravenösen und intrakoronaren Applikation sowie Verfahren zu ihrer Herstellung | |
DE102009003980A1 (de) | Propofol in triheptanoinhaltiger Trägeremulsion | |
DE3873684T2 (de) | Lipidemulsion und verfahren zur intravenoesen infusion. | |
WO2000016770A1 (fr) | Preparation pharmaceutique contenant du taxane et procede de preparation d'une telle composition | |
DE69113391T2 (de) | Fettige Emulsion. | |
WO2021123117A1 (fr) | Procédé de production d'émulsions huile dans l'eau |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PT RO SE SI SK TR |
|
AX | Request for extension of the european patent |
Extension state: AL LT LV MK |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN |
|
18W | Application withdrawn |
Effective date: 20050128 |